mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.
mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.
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mRNA疫苗会诱导SARS-COV-2和关注的变体诱导耐用的免疫记忆。
DOI：
10.1126/science.abm0829
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发表时间：
2021-12-03
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事实证明，接种严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）疫苗对预防严重COVID-19非常有效。然而，随着时间的推移，病毒变异的进化和抗体水平的下降，对疫苗诱导的免疫保护的寿命提出了疑问。Goel等人检测了接受SARS-CoV-2信使RNA疫苗个体的B淋巴细胞和T淋巴细胞反应。他们对从未感染过SARS-CoV-2的人与从SARS-CoV-2中康复的人进行了为期6个月的纵向研究。在接种疫苗的个体中观察到体液和细胞免疫记忆，以及针对α (B.1.1.7)、β (B.1.351)和Delta （B.1.617.2）病毒变体的功能性免疫反应。对T细胞活性的分析表明，强大的细胞免疫记忆可能通过限制严重疾病的发展来预防住院。现代SARS-CoV-2 mRNA疫苗接种个体的pnk血液分析揭示了不同的免疫记忆反应轨迹。严重急性呼吸综合征冠状病毒2 (SARS-CoV-2) mRNA疫苗在预防感染特别是严重疾病方面非常有效。然而，关注变体（VOCs）的出现和接种疫苗个体感染的增加引发了对接种后免疫持久性的质疑。为了研究免疫记忆，我们纵向分析了61名接受mRNA疫苗的个体从基线到接种后6个月的抗原特异性抗体、记忆B细胞和记忆T细胞反应。一个由16人组成的亚组已经从先前的SARS-CoV-2感染中恢复过来，这为用mRNA疫苗增强先前存在的免疫力提供了新的见解。在接种mRNA疫苗后6个月，大多数个体的抗刺突、抗受体结合域（RBD）和中和抗体仍高于疫苗前基线水平，尽管抗体确实随着时间的推移而下降。mRNA疫苗接种也产生了刺突和rbd特异性记忆B细胞，包括与α、β和δ rbd交叉结合的记忆B细胞，这些记忆B细胞在刺激后能够快速产生功能性抗体。值得注意的是，接种疫苗后3至6个月，sars - cov -2特异性记忆B细胞的频率继续增加。mRNA疫苗也比单纯轻度SARS-CoV-2感染产生更高频率的变异型交叉结合记忆B细胞，在6个月时，rbd特异性记忆B细胞交叉结合所有三种挥发性有机化合物的比例为50%。这些变异结合记忆B细胞比仅野生型结合细胞更容易发生超突变。在第二次疫苗剂量后，sars - cov -2特异性记忆CD4+和CD8+ T细胞反应从峰值水平下降，sars - cov -2特异性记忆CD4+ T细胞在3至6个月内相对稳定。第一次疫苗剂量后的T滤泡辅助细胞反应与6个月时的抗体相关，突出了早期CD4+ T细胞反应的关键作用。最后，先前存在免疫的个体对mRNA疫苗接种的回忆反应导致循环抗体滴度的增加，这与先前存在的记忆B细胞频率相关。然而，记忆B细胞和T细胞的长期频率没有显著增加。SARS-CoV-2-naïve与接种疫苗后恢复的受试者的抗体衰减率也没有显著差异，这表明对mRNA疫苗接种的回忆反应的主要好处可能是循环抗体的强劲但短暂的增加。这些发现证明了接种SARS-CoV-2 mRNA后的多组分免疫记忆，即使抗体下降，记忆B和T细胞反应仍然持久。免疫记忆对挥发性有机化合物具有弹性，并在抗原再暴露时产生有效的回忆反应。尽管抗体逐渐减少，但这些持久的记忆细胞可能对接种疫苗的个体持续抵抗严重疾病负责。我们的数据也可以告知对加强疫苗接种的免疫结果的期望。在接种疫苗后的六个时间点测量了sars - cov -2特异性抗体、记忆B和记忆T细胞反应，强调了持久免疫记忆的协调进化。B细胞记忆也对挥发性有机化合物具有弹性，并且能够在重新激活时产生新的抗体。IgG，免疫球蛋白G；Ab抗体;NTD， n端域；TFH， T滤泡辅助细胞；WT,野生型。严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）信使RNA （mRNA）疫苗接种后免疫记忆的持久性尚不清楚。在这项研究中，我们在接种疫苗6个月后纵向分析了SARS-CoV-2-naïve和康复个体的疫苗反应。抗体从峰值水平下降，但在大多数受试者6个月时仍可检测到。相比之下，mRNA疫苗产生的功能记忆B细胞在接种后3至6个月增加，其中大多数细胞交叉结合α、β和δ变体。mRNA疫苗进一步诱导抗原特异性CD4+和CD8+ T细胞，早期CD4+ T细胞应答与长期体液免疫相关。已有免疫力的个体对疫苗接种的回忆反应主要是增加抗体水平，而没有实质性改变抗体衰减率。总之，这些发现表明，在mRNA疫苗接种后至少6个月，细胞对SARS-CoV-2及其变体具有强大的免疫记忆。
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven highly effective at preventing severe COVID-19. However, the evolution of viral variants, and waning antibody levels over time, raise questions regarding the longevity of vaccine-induced immune protection. Goel et al. examined B and T lymphocyte responses in individuals who received SARS-CoV-2 messenger RNA vaccines. They performed a 6-month longitudinal study of individuals who never had SARS-CoV-2 infection compared with people who had recovered from SARS-CoV-2. Humoral and cellular immune memory was observed in vaccinated individuals, as were functional immune responses against the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) viral variants. Analysis of T cell activity suggested that robust cellular immune memory may prevent hospitalization by limiting the development of severe disease. —PNK Blood analysis of individuals vaccinated with the Moderna SARS-CoV-2 mRNA vaccine reveals distinct trajectories of immune memory responses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are highly effective at preventing infection and especially severe disease. However, the emergence of variants of concern (VOCs) and increasing infections in vaccinated individuals have raised questions about the durability of immunity after vaccination. To study immune memory, we longitudinally profiled antigen-specific antibody, memory B cell, and memory T cell responses in 61 individuals receiving mRNA vaccines from baseline to 6 months postvaccination. A subgroup of 16 individuals had recovered from prior SARS-CoV-2 infection, providing insight into boosting preexisting immunity with mRNA vaccines. mRNA vaccination induced robust anti-spike, anti–receptor binding domain (RBD), and neutralizing antibodies that remained above prevaccine baseline levels in most individuals at 6 months postvaccination, although antibodies did decline over time. mRNA vaccination also generated spike- and RBD-specific memory B cells, including memory B cells that cross-bound Alpha, Beta, and Delta RBDs, that were capable of rapidly producing functional antibodies after stimulation. Notably, the frequency of SARS-CoV-2–specific memory B cells continued to increase from 3 to 6 months postvaccination. mRNA vaccines also generated a higher frequency of variant cross-binding memory B cells than mild SARS-CoV-2 infection alone, with >50% of RBD-specific memory B cells cross-binding all three VOCs at 6 months. These variant-binding memory B cells were more hypermutated than wild-type–only binding cells. SARS-CoV-2–specific memory CD4+ and CD8+ T cell responses contracted from peak levels after the second vaccine dose, with relative stabilization of SARS-CoV-2–specific memory CD4+ T cells from 3 to 6 months. T follicular helper cell responses after the first vaccine dose correlated with antibodies at 6 months, highlighting a key role for early CD4+ T cell responses. Finally, recall responses to mRNA vaccination in individuals with preexisting immunity led to an increase in circulating antibody titers that correlated with preexisting memory B cell frequency. However, there was no substantial increase in the long-term frequency of memory B and T cells. There was also no significant difference in the decay rates of antibodies in SARS-CoV-2–naïve versus –recovered subjects after vaccination, which suggests that the main benefit of recall responses to mRNA vaccination may be a robust but transient increase in circulating antibodies. These findings demonstrate multicomponent immune memory after SARS-CoV-2 mRNA vaccination, with memory B and T cell responses remaining durable even as antibodies decline. Immune memory was resilient to VOCs and generated an efficient recall response upon antigen reexposure. These durable memory cells may be responsible for continued protection against severe disease in vaccinated individuals, despite a gradual reduction in antibodies. Our data may also inform expectations for the immunological outcomes of booster vaccination. SARS-CoV-2–specific antibody, memory B, and memory T cell responses were measured at six time points after vaccination, highlighting a coordinated evolution of durable immunological memory. B cell memory was also resilient to VOCs and capable of producing new antibodies upon reactivation. IgG, immunoglobulin G; Ab, antibody; NTD, N-terminal domain; TFH, T follicular helper cell; WT, wild-type. The durability of immune memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination remains unclear. In this study, we longitudinally profiled vaccine responses in SARS-CoV-2–naïve and –recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. By contrast, mRNA vaccines generated functional memory B cells that increased from 3 to 6 months postvaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with preexisting immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.
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影响因子：
8.7
作者：
Corrie BD;Marthandan N;Zimonja B;Jaglale J;Zhou Y;Barr E;Knoetze N;Breden FMW;Christley S;Scott JK;Cowell LG;Breden F
通讯作者：
Breden F
影响因子：
32.4
作者：
Dugan HL;Stamper CT;Li L;Changrob S;Asby NW;Halfmann PJ;Zheng NY;Huang M;Shaw DG;Cobb MS;Erickson SA;Guthmiller JJ;Stovicek O;Wang J;Winkler ES;Madariaga ML;Shanmugarajah K;Jansen MO;Amanat F;Stewart I;Utset HA;Huang J;Nelson CA;Dai YN;Hall PD;Jedrzejczak RP;Joachimiak A;Krammer F;Diamond MS;Fremont DH;Kawaoka Y;Wilson PC
通讯作者：
Wilson PC
影响因子：
64.8
作者：
Gaebler C;Wang Z;Lorenzi JCC;Muecksch F;Finkin S;Tokuyama M;Cho A;Jankovic M;Schaefer-Babajew D;Oliveira TY;Cipolla M;Viant C;Barnes CO;Bram Y;Breton G;Hägglöf T;Mendoza P;Hurley A;Turroja M;Gordon K;Millard KG;Ramos V;Schmidt F;Weisblum Y;Jha D;Tankelevich M;Martinez-Delgado G;Yee J;Patel R;Dizon J;Unson-O'Brien C;Shimeliovich I;Robbiani DF;Zhao Z;Gazumyan A;Schwartz RE;Hatziioannou T;Bjorkman PJ;Mehandru S;Bieniasz PD;Caskey M;Nussenzweig MC
通讯作者：
Nussenzweig MC
DOI：
10.1038/s41577-021-00522-1
发表时间：
2021-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Carvalho T;Krammer F;Iwasaki A
通讯作者：
Iwasaki A
DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G